ASCITIC INTERLEUKIN-12 IS AN INDEPENDENT PROGNOSTIC FACTOR IN OVARIAN-CANCER

Purpose: The clinical impact of endogenous cytokines supplied with det erministic properties in the generation of either T helper (Th)1-type or Th2-type immune response was investigated in patients with ovarian cancer. Whereas interleukin (IL)-12 initiates the differentiation of n aive ThO cells toward Th1 phenotype, IL-4 and IL-10 mediate the develo pment of Th2-type immunity, Patients and Methods: Cytokines were deter mined before treatment by means of enzyme-linked immunosorbent assay ( ELISA) in ascites fluid and serum of 76 patients with ovarian cancer. Cytokine levels were compared with each other and with standard clinic opathologic parameters. A stepwise logistic regression was calculated to rule out interdependence in the associations of the various variabl es, Survival analyses were performed with the Kaplan-Meier method and differences in survival were examined according to Mantel and Breslow. Cox proportional hazards analysis was used to identify independent pr ognostic factors. Results: Whereas IL-10 and IL-12 were detectable in all ascites-fluid samples, IL-4 was measurable in only 43% of the spec imens. With the exception of neopterin, macrophage colony-stimulating factor (M-CSF), and IL-4, determined cytokine levels were significantl y elevated in ascites fluid compared with serum (P < .01), In univaria te analyses, high ascitic-fluid concentrations of either neopterin, hu mor necrosis factor-alpha (TNF-alpha), or IL-12 were associated with p oor disease-free (P < .005) and overall (P < .01) survival, Multivaria te Cox regression analysis showed ascitic-fluid IL-12 levels to be the only immunologic variable that retained independent prognostic signif icance (P < .03 for disease-free and P < .01 for overall survival), to gether with residual disease, Federation Internationale de Gynecologie et d'Obstetrique (FIGO)-stage, and patient age, Conclusion: In ovaria n cancer, high ascitic-fluid IL-12 levels, which may indicate a local Th1-generated immune response, are associated with disease progression .